Abstract
Inflammation is thought to be involved in the pathophysiology of bipolar disorder (BP) and metabolic syndrome. Prior studies evaluated the association between metabolic profiles and cytokines only during certain mood states instead of their changes during treatment. We enrolled drug-naïve patients with BP-II and investigated the correlation between changes in mood symptoms and metabolic indices with changes in plasma cytokine levels after 12 weeks of pharmacological treatment. Drug-naïve patients (n = 117) diagnosed with BP-II according to DSM-IV criteria were recruited. Metabolic profiles (cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI) and plasma cytokines (TNF-α, CRP, IL-6, and TGF-β) were measured at baseline and 2, 8, and 12 weeks post-treatment. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0%) patients completed the intervention. Changes in plasma CRP were significantly associated with changes in BMI (P = 1.7E-7) and triglyceride (P = 0.005) levels. Changes in plasma TGF-β1 were significantly associated with changes in BMI (P = 8.2E-6), cholesterol (P = 0.004), and triglyceride (P = 0.006) levels. However, changes in plasma TNF-α and IL-6 were not associated with changes in any of the metabolic indices. Changes in Hamilton Depression Rating Scale scores were significantly associated with changes in IL-6 (P = 0.003) levels; changes in Young Mania Rating Scale scores were significantly associated with changes in CRP (P = 0.006) and TNF-α (P = 0.039) levels. Plasma CRP and TGF-β1 levels were positively correlated with several metabolic indices in BP-II after 12 weeks of pharmacological intervention. We also hypothesize that clinical symptoms are correlated with certain cytokines. These new findings might be important evidence that inflammation is the pathophysiology of clinical symptoms and metabolic disturbance in BP-II.Trial RegistrationClinicalTrials.gov NCT01188148.
Highlights
Bipolar II disorder (BP-II), defined as recurrent episodes of depression and hypomania, is frequently misdiagnosed in clinical settings [1,2,3,4]
DSM-IV-TR [42] criteria require a minimum duration of 4 days of hypomania, current epidemiologic data samples [2,7,43,44,45,46] suggest that a 2-day duration is more prevalent in the community; we used the 2-day minimum for hypomania when diagnosing BP-II
All patients with BP-II were first diagnosed, and that they had no history of taking mood stabilizers or antipsychotics was verified
Summary
Bipolar II disorder (BP-II), defined as recurrent episodes of depression and hypomania, is frequently misdiagnosed in clinical settings [1,2,3,4]. The high rate of suicide in BP-II may be explained by frequent misdiagnoses of the disorder followed by ineffective treatment [11,12]. Activation of the inflammatory response system and increased activity of the proinflammatory cytokines interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor (TNF-a) were found during acute manic and depressive states [14,15] [16,17,18]. Whether these phenomena are state-dependent and normalize in remission remains controversial [19,20]. An understanding of an association between inflammation and BP might reveal novel pathophysiology and treatment options, and it might even benefit investigating using anti-inflammatory medications to treat BP [21,22]
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